An alarming new superbug may be on its way — an incurable form of gonorrhea. The disease, once easily killed with a shot of penicillin, is increasingly becoming drug-resistant. Soon, the world may face a version that can’t be killed by any known antibiotic, warned Catherine Ison, the director of the sexually transmitted bacteria reference library with the United Kingdom’s Health Protection Agency.

In recent years, as the disease has evolved, medications once proven to kill the bacteria have become less effective except one, a class of antibiotics called cephalosporins. Now some strains of gonorrhea are showing signs of being resistant to even that, Ison told those at a scientific meeting last week in Edinburgh, Scotland.

"If this problem isn't addressed, there's a very real possibility that gonorrhea will become a very difficult infection to treat," she said.

Gonorrhea is the second most commonly reported infectious disease in the United States. In 2008, there were 336,742 official cases, but this number, the most recent available from the Centers for Disease Control and Prevention, may vastly underestimate the true number.

“We will probably have something like 700,000 cases of gonorrhea this year,” suggested Dr. Edward W. Hook, professor of medicine at the University of Alabama at Birmingham and an expert on STD infections.

Not all of those who are infected know it, contributing to the problem. Undiagnosed cases, or infections that are unsuccessfully treated and then linger without obvious symptoms, can create serious health problems. For example, teenage girls between 15 and 19 account for more cases than any other age group. If they aren’t cured, they risk pelvic inflammatory disease, infertility or ectopic pregnancies. People infected with gonorrhea are also about three times more likely to become infected with HIV should they come into contact with the virus.

“The other major cost is infection of children born to infected mothers,” Hook explained. “And rarely you can get gonorrheal infections of heart valves, and arthritis.”

History of being hard to treatGonorrhea has a long history of evading medicine’s attempts to cure it. In the 1930s, sulfa-based drugs worked, but soon lost potency as the bacteria adapted. Penicillin came up to bat in the 1940s. In New York City, Los Angeles, and points in between, posters appeared stating “Penicillin Cures Gonorrhea in 4 Hours,” sometimes underneath words urging citizens to buy war bonds to “Thrash the Axis.”

Just as defeating Hitler and the Japanese emperor had become an all-consuming national priority, health officials, armed with the new miracle drug penicillin, offered hope that the scourge of “VD” could be wiped out, too.

Penicillin was a miracle, but eventually doctors had to use more and more to kill the bug. Still, a shot of penicillin remained the treatment of choice until 1985, when rising resistance to penicillin, and the fact that many people are allergic to it, forced health officials to give other antibiotics their turns.

But as they did, strains of the bacteria morphed to make the antibiotics less effective. A February report from a group of Taiwanese doctors found that during the five years between 1999 and 2004, 40 percent of gonorrhea isolated from their patients was resistant to penicillin, tetracycline, erythromycin and ciprofloxacin, all drugs which used to kill off gonorrhea like magic bullets.

Rates of women who are opting for preventive mastectomies, such as Angeline Jolie, have increased by an estimated 50 percent in recent years, experts say. But many doctors are puzzled because the operation doesn't carry a 100 percent guarantee, it's major surgery -- and women have other options, from a once-a-day pill to careful monitoring.

In May of 2009, doctors at Sydney, Australia’s Prince of Wales Hospital reported two cases of failed treatment of gonorrhea of the pharynx (typically resulting from oral sex or oral-anal contact). The drug they used is called ceftriaxone, a cephalosporin given by injection. There have also been scattered reports of increasing drug resistance to the most commonly used pill form of cephalosporin, although not in the U.S. so far, said Dr. Kimberly Workowski, associate professor of medicine at Emory University and the CDC’s coordinator of STD treatment guidelines. The CDC monitors the issue through its Gonorrhea Isolate Surveillance Project which receives reports from health clinics all over the country.

Workowski is concerned, though. For one thing, some people who are allergic to penicillin may also be allergic to cephalosporins.

Since people with some forms of gonorrhea may not show symptoms, their partners may have no idea they're infected. The pill form of cephalosporin, which can be used for uncomplicated rectal or urogenital infections, is “only 70 percent effective” in treating pharyngeal gonorrhea, she noted. Since infection of the pharynx often carries no symptoms, people treated for urogenital infection may not know they carry a pharyngeal infection, too. That gives the disease a safe harbor from which it can launch infections of more people.

Resistance has tended to follow geography and sexual orientation, Workowski explained. “Traditionally southeast Asia has developed resistant isolates and then there is a slow spread across [the Pacific], eventually coming to the U.S.,” she said. Resistant strains also tend to show up first in men who have sex with men.

Other drug-resistant STDsResistance could also become an issue in other bacterial STDs. About 30 percent of females who contract gonorrhea are co-infected with chlamydia. While chlamydia seems to respond well to medication so far, a small number of strains have shown signs of developing drug-resistance, says Workowski. Hook, however, says he doesn’t know of any resistant strains.

Syphilis has already defeated one drug used to treat it, azithromycin. Between 2000 and 2004, the prevalence of azithromycin-resistant syphilis in one San Francisco clinic jumped from zero percent to 56 percent.

“We have since been looking at azithromycin mutations in strains from all over the country and world,” said Sheila Lukehart, research professor of medicine at the University of Washington and an author of the New England Journal of Medicine report about the San Francisco clinic. “We’ve found a very a broad distribution of the specific mutation that gives syphilis antibiotic resistance.”

The good news is that penicillin still works against syphilis; the treatment consists of two shots, one in each butt cheek. No credible data suggests that syphilis has been able to adapt to penicillin, probably, Lukehart explained, because penicillin attacks a critical site on the bacterium that is so crucial to the bug’s survival that it can’t change it. Still, the loss of azithromycin makes infections tough to treat in people allergic to penicillin since they must be desensitized — often in a hospital — and then treated.

'Doomsday scenario'There are alternatives should gonorrhea prove resistant to the cephalosporins. While a sudden change in the gonorrhea bacteria that leaves it completely resistant to the cephalosporins would be “the doomsday scenario,” Hook said, it’s more likely that the evolution will be gradual. So following the old strategy of increasing doses as the resistance increases will buy time. He also holds out hope that pharmaceutical companies, which see antibiotic development as unprofitable, will suddenly have a big incentive to create new drugs should the cephalosporins lose their effectiveness.

Meanwhile, the CDC is developing other strategies. It is about to start a trial, operated through the National Institutes of Health, to look at alternative therapies like giving patients a one-two punch of an oral and an intramuscular injection using two different classes of antibiotics at once. Doctors already routinely treat female gonorrhea patients with a different drug for Chlamydia on the assumption they’ll be infected with it, too. Ideally, though, researchers will find either a new drug, or prove an existing antibiotic will work.

Of course, it’s better to prevent an infection in the first place. Being tested for STDs and using condoms, the same techniques the military promoted among the troops to fight “VD” back in World War II before penicillin, are still the best bacterial STD fighters of all.